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- W2981678042 abstract "Multiple primary lung cancer (MPLC) is a presumed uncommon entity, but its true incidence, ranging from 0.2% to 8%, is increasing as the result of the widespread use of early detection tools. MPLC displays diverse clinical trajectories and genomic profiles. The in-depth study on the mechanism of malignant transformation of MPLC will provide new ideas for the future treatment of MPLC. In this study, we analyse the genomic profiles of 25 tumors and 12 adjacent tissues from 10 patients with MPLC who underwent surgical resection through the whole-exome sequencing (WES). Ten patients were enrolled in this study, one patient with different evolutional stages of the same disease (AAH, MIA, and IA) and one patient with completely different pathologies (adenocarcinoma and squamous cancer). Eight patients with different driver genes (EGFR exon 19 deletion, exon 21 L858R mutation and exon 21 L861Q mutation) of lung adenocarcinoma. We observed different mutational landscapes between tumors in the same patient by analyzing somatic mutations, copy number variations, clonal structures, and signal transduction pathways. Most tumors showed significant APOBEC mutant patterns, especially C→T transversions (Figure 1). Moreover, we also found that EGFR exon 19 and 21 mutations enrich different signal pathways. The PI3K/AKT signal pathway is often be enriched in tumors with EGFR exon 19 deletion, which is closely related to the early progression of the tumor. While PTEN kinase activation is associated with EGFR exon 21 L858R mutation (Figure 2). MPLCs with EGFR wild-type may be associated with abnormal regulation of signal pathways, including SOS1, JAK-STAT and others.View Large Image Figure ViewerDownload Hi-res image Download (PPT) This study suggests that the different gene mutation trajectories of EGFR exon 19 and 21 mutations are closely related to the genetic heterogeneity of MPLC. Besides that，APOBEC mediated mutations may play an important role in the initial malignant transformation of tumors." @default.
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- W2981678042 date "2019-10-01" @default.
- W2981678042 modified "2023-10-17" @default.
- W2981678042 title "P2.03-46 PI3K/AKT Signal Pathway Regulates Malignant Transformation of MPLC with EGFR-Sensitive Mutation" @default.
- W2981678042 doi "https://doi.org/10.1016/j.jtho.2019.08.1493" @default.
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